| Operation is the main treatment of surgical department, which is a behavior to damage tissue integrity or to recover damaged tissue. In operative treatment, the most common adverse reaction was pain. Postoperative pain is not only a great deal of suffering to patients, it can also cause a variety of adverse changes in blood pressure and heart rate. Because of adverse effects on the prognosis of patients caused by postoperative pain,it being taken seriously by the clinical. postoperative pain, breathing, body temperature, pulse, blood pressure were defined jointly the five vital signs to maintain the body’s normal activity by medical profession. Effective treatment of postoperative pain is of great significance in the clinical.Parecoxib Sodium is a specific COX-2 inhibitors developed by Pharmacia,it is the first COX-2 inhibitors which can be administered by intravenous and intramuscular injection. After approved by the Danish listed in March 2002, the drug also received approval to market by the Czech Republic and the Netherlands. April 2002 listed in all 15 EU countries plus Norway and Iceland. December 2004, parecoxib sodium approved listed in Taiwan. March 2008 listed in China. Parecoxib sodium as soluble pro-drug of valdecoxib, it can be administered by intravenous or intramuscular injection, hydrolysis in the liver, and converted into pharmacological valdecoxib quickly, inhibition of COX-2 specific for analgesic effects, it also prevents the central and peripheral sensitization for preemptive analgesia. Parecoxib sodium single intravenous or intramuscular injection of 20 mg,almost completely converted to valdecoxib rapidly in the body, the plasma half-life about 22 minutes. About 30 minutes or 1 hour after injection respectively, Valdecoxib reach peak concentration, mainly eliminate in the liver, less than 5% of valdecoxib excretion through urine in prototype form. After intravenous or intramuscular, valdecoxib elimination half-life(t1/2) is X approximately 8 hours. Parecoxib efficacy in the treatment of postoperative pain, has been demonstrated in a variety of types of surgery, the exact effect and safety, can be administered by injection, has been widely used in clinical practice.To improve product quality and reduce costs, the author make selections of synthetic route of Parecoxib Sodium and optimized its synthesis process, the final product quality has already qualified to the original research standards.Synthesis, analysis and preparation work of related impurities are under investigation.1ã€The choice of synthesis route of Parecoxib SodiumThrough lots of literature research and experimental study, the author select and improve a reaction route. This route used 1,2-Diphenylethanone as starting material, through condensation, cyclization, dehydration, sulfonamides reaction, propionyl, Salt-forming reaction obtain the final product. The final product and its main intermediates were all pass the constitution’s confirmation by HPLC, 1H-NMR, 13C-NMR, IR and other structural confirmation..2ã€Improvement on synthetic technology of Parecoxib SodiumIn this paper, the reaction process was investigated and researched. The author respectively discussed every factor which influences the reaction results, judged and studied on the optimization of the reaction process and after-treatment. Finally, it defines the most optimal process conditions that make the reaction process simply, the operation easily and the quality controllable. When synthesis of 4,5-dihydro-5-methyl-3,4-diphenyl-5isoxazole, using LDA as catalyst, the reaction conditions are mild, safe and reliable; When synthesis of 5-methyl-3,4-diphenyl-5-isoxazolyl, using TFA as catalyst, the yield of about 20% than sulfuric acid as catalyst; when synthesis of valdecoxib, investigated process parameters and solvent for purification, improve the key intermediate yields nearly doubled, single impurity less than 0.1%; when synthesis parecoxib, it is determined using the acid-catalyzed reactions, acetone-water to purification, improved the reaction yield, and ensure the quality of the key intermediate.3ã€ConclusionIn this paper, author redesigns the reaction route, and improves the process. The improved method has the advantages of simple operation, mild reaction conditions, appropriate cost and controllable quality. It is suitable for industrialized production. The total yield is about 24.20%, and the purity of the final product is about 99.98%. The total impurities content is less than ten permill, and single impurity content is less than one permill. It has already qualified to the original research drug standard. The result provides a solid basis for following research work. |
